COVID-19 Biochemistry

1. BIOCHEMICAL BIOMARKERS ALTERATIONS IN
CORONAVIRUS DISEASE 2019 (COVID-19)
DR.ANITA VERMA
MBBS(MAMC,DELHI)
MD(SMS MC,JAIPUR)
PROFESSOR,
BIOCHEMISTRY,SPMC,BIKANER

2. • The severe acute respiratory syndrome
Coronavirus 2 (SARS-CoV-2), which belongs to
the Coronaviridae family, causes a highly
transmittable acute respiratory disease,
defined by the World Health Organization
(WHO) as Coronavirus Disease 2019 (COVID-
19).

3. • The first cases of COVID-19 were detected in
Wuhan, Hubei Province, People’s Republic of
China, at the end of 2019. Since then, the
illness spread rapidly around the country and
the world reaching a pandemic level.
• On 30 January 2020, the WHO declared the
outbreak of COVID-19 to be a “public health
emergency of international concern”.

4. Biochemical profiles alterations
According to the severity of the disease, the
clinical course of COVID-19 can be classified
into three stages, namely
 Early infection
 Pulmonary phase
 Hyperinflammation phase
each one characterised by specific
biochemical alterations.

6. • The first stage occurs at the time of the infiltration of the virus
in the lung parenchyma, where SARS-CoV-2 infects ciliated
bronchial epithelial cells through the interaction with the
angiotensin-converting enzyme 2 (ACE2).
• ACE2 is a monocarboxypeptidase with a critical role in
regulating the cleavage of several peptides within the renin-
angiotensin system. It is highly expressed on pneumocytes in
the lung.
• At this stage, most of the patients present non-specific
symptoms, such as dry cough and fever, associated with an
initial inflammatory response due to the innate immunity,
mainly monocytes and macrophages. Lymphocytopenia is a
hallmark of this stage.

7. • The pulmonary phase is characterised by
established pulmonary disease (viral
pneumonia), associated with localised
inflammation within the lung. Biochemical
characteristics include lymphopenia and an
increase of transaminases as well as systemic
inflammation biomarkers, such as C-reactive
protein (CRP). At this stage, most of the
patients require hospitalization.

8. • The third stage of COVID-19 is the most severe,
characterised by systemic inflammation, or cytokine
storm, leading to ARDS and MOF. At this stage,
patients should be admitted to an Intensive Care
Unit (ICU). Several inflammatory biomarkers are
significantly increased. Moreover, most of the
patients present cardiac and kidney injury, which can
be detected by circulating biomarkers. Also,
alterations of the central nervous system (CNS).

10. Main biochemical alterations in
severe COVID-19 patients
HAEMATOLOGICAL
↓ Lymphocyte count
↑ Neutrophil count
↑ NLR (neutrophil lymphocyte ratio)
↓ Platelet count

11. • Lymphopenia represents the most common laboratory finding detected at
the cell blood count (CBC) in COVID-19 patients, since the initial stage of
early infection.
• As showed for SARS-CoV, it has been hypothesized that the virus might
directly infect lymphocytes, principally T cells, inducing depletion of
CD4+ and CD8+ cells and, thus, suppressing the cellular immune response.
• The evidence that lymphocytes express the ACE2 receptor on their cellular
membrane supports such a hypothesis. Additionally, the virus might
directly destroy lymphatic organs. However, this hypothesis needs to be
confirmed by the evidence of pathological dissection in such organs.
Finally, pro-inflammatory cytokines, such as IL-6 and TNF-alpha, could
induce lymphocyte deficiency

12. INFLAMMATORY
↑ ERS
↑ CRP
↑ PCT
↑ IL-6
↑ LDH
↑ MDW

13. • The hallmark of severe COVID-19 is the
hyperinflammatory host response due to the
so-called “cytokine storm”, defined as an
uncontrolled systemic inflammatory response
due to the release of large amounts of pro-
inflammatory cytokines, resulting from the
SARS-CoV-2 induced activation of both natural
and cellular immunity.

14. COAGULATION
• ↑ D-dimer
↑ FDP
↑ PT
↑ aPTT
↑ Fibrinogen

15. • A hypercoagulable state, which might promote thrombotic
coagulopathies such as pulmonary microthrombosis and
disseminated intravascular coagulation (DIC), is a common
complication of severe COVID-19.
• The underlying pathological mechanisms include infection-
related dysfunction of endothelial cells, which causes an
increased production of thrombin and inhibition of the
fibrinolysis; cardiovascular injury; hyperinflammation state;
prolonged immobilisation due to the illness; mechanical
ventilation; and central venous catheters.

16. ELECTROLYTE
↓ K+
↓ Na+
↓ Ca++

17. • Some authors described alterations of electrolyte
levels, including sodium, potassium, chloride, and
calcium, in COVID-19 patients. Specifically,
hyponatremia, hypokalemia, and hypocalcemia have
been associated with severe disease. Although
pathophysiological mechanisms underlying such
alterations are not fully understood yet, some
hypotheses have emerged. The interaction of SARS-
Cov-2 with ACE2 receptor might reduce ACE2
expression, resulting in an increased angiotensin II,
which promote potassium excretion, leading to
hypokalemia.

18. HEPATIC
↑Alanine aminotransferase
↑ Aspartate aminotransferase
↑ Total bilirubin
↓ Albumin

19. • The alteration of hepatocytes damage biomarkers, such as
aspartate aminotransferase (AST), alanine aminotransferase
(ALT), bilirubin, and albumin, is a common laboratory finding
in COVID-19 patients. However, the underlying mechanism is
not fully understood. Although hepatocytes and bile duct
epithelial cells express ACE2 receptor, no significant altered
histopathological features have been detected in such cells
from COVID-19 patients. Thus, COVID-19-related liver
dysfunction could be the result of secondary liver damage due
to the administration of hepatotoxic drugs, systemic
inflammatory response, respiratory distress syndrome-
induced hypoxia, and MOF

20. MUSCULAR
↑ CK
↑ Mioglobin

21. • COVID-19 patients typically present increased
levels of biomarkers of muscle injury, namely
creatine-kinase (CK) and myoglobin. However,
the alterations of such biomarkers could be
the result of several clinical conditions,
including kidney dysfunction and cardiac
injury, or a direct effect of the SARS-CoV-2,
which can also infect cells of the muscle tissue
due to the expression of the ACE2 receptor.

22. RENAL
↑ Creatinine
CARDIAC
↑ cTn
↑ BNP/nt-proBNP

23. • Several studies reported kidneys alterations,
as reflected by increased serum creatinine, in
COVID-19 patients. SARS-CoV-2 could directly
infect kidney tubular cells, which express the
ACE2 receptor on their cellular surface.
Moreover, circulating mediators could interact
with kidney-resident cells resulting in
endothelial dysfunction, microcirculatory
derangement, and tubular injury

24. CONCLUSIONS
• Laboratory medicine has a crucial role for the
appropriate COVID-19 management since the early
recognition to the assessment of disease severity and
the prediction risk of evolution towards severe
disease, characterised by the impairment of several
organs and tissues. The latter can be due to both
indirect and direct effects of SARS-CoV-2 infection.
Indeed, the virus can infect cells through the
interaction with the ACE2 receptor, which is highly
expressed in many organs and tissues.

25. THANKS